Quantification of age‐related changes of α‐tocopherol in lysosomal membranes in murine tissues and human fibroblasts

Abstract

Considering the biological function of α‐tocopherol (α‐Toc) as a potent protective factor against oxidative stress, this antioxidant is in the focus of aging research. To understand the role of α‐Toc during aging we investigated α‐Toc concentrations in young and aged primary human fibroblasts after supplementation with RRR‐α‐Toc. Additionally, α‐Toc contents were determined in brain, kidney, and liver tissue of 10 week‐, 18 month‐, and 24 month‐old mice, which were fed a standard diet containing 100 mg/kg dl‐α‐tocopheryl acetate. α‐Toc concentrations in isolated lysosomes and the expression of the α‐Toc transport proteins Niemann Pick C1 (NPC1), Niemann Pick C2 (NPC2), and lipoprotein lipase were also analyzed. Obtained data show a significant age‐related increase of α‐Toc in murine liver, kidney, and brain tissue as well as in human dermal fibroblasts. Also liver and kidney lysosomes are marked by elevated α‐Toc contents with aging. NPC1 and NPC2 protein amounts are significantly decreased in adult and aged murine kidney tissue. Also aged human dermal fibroblasts show decreased NPC1 amounts. Supplementation of young and aged fibroblasts led also to decreased NPC1 amounts, suggesting a direct role of this protein in α‐Toc distribution. Our results indicate an age‐dependent increase of α‐Toc in different murine tissues as well as in human fibroblasts. Furthermore saturation and intracellular distribution of α‐Toc seem to be strongly dependent on the availability of this vitamin as well as on the presence of the lysosomal protein NPC1. © 2016 BioFactors, 42(3):307–315, 2016

The Aging Lacrimal Gland of Female C57BL/6J Mice Exhibits Multinucleate Macrophage Infiltration Associated With Lipid Dysregulation

“… 16 The cholesterol transporters Niemann–Pick disease type C1 (NPC1), and Niemann–Pick disease type C2 (NPC2) are dysregulated in aging. 17 – 19 NPC1 is a transmembrane protein that mediates intracellular cholesterol trafficking, and NPC2 is a soluble protein that functions in egressing and recycling of lipoprotein-derived cholesterol. 20 – 22 Dysregulation of these enzymes is linked to lipid accumulation in atherosclerosis and age-related macular degeneration.…”